Amanda Barry, a doctoral student in the department of environmental and biomolecular systems at OHSU's Division of Environmental and Biomolecular Systems, has received the Igor Stojiljkovic Memorial Fellowship award for best graduate student presentation at the 2006 Biometals Symposium. Barry's presentation examined the copper-binding site of the copper chaperone for superoxide dismutase.

2006 was the fifth year of the Biometals conference, an international Symposium presenting advances in the understanding of metal transport and regulation held this year in Welches, Oregon. It was the first year, however, for the Stojiljkovic Memorial Fellowship. The award was named after Igor Stojiljkovic, a young scientist at Emory University who studied iron transport systems in Neisseria, the genus of bacteria which includes the species N. gonorrhoeae which causes gonorrhoea, and N. meningitidis, one of the most common causes of bacterial meningitis. Dr. Stojilkovic died in 2003, and the Memorial Fellowship which bears his name honors promising young graduate student and post-doctoral investigators engaged in biometals research. It is accompanied by a $1,000 prize.

Barry's presentation was titled, "Probing the Active Cluster In Human Copper Chaperone For Superoxide Dismutase With Selenocysteine Variants." Her research, designed to improve understanding of copper transport in human cells, involved the construction of selenocysteine-containing mutants of the human copper chaperone for superoxide dismutase using intein-mediated peptide ligation. After their construction, the mutants were studied with respect to their ability to transfer copper to superoxide dismutase and their copper-binding and X-ray absorption spectroscopic properties.

In her presentation, Barry noted that previous studies have outlined three distinct polypeptide domains in the copper chaperone for superoxide dismutase--an enzyme which catalyzes an important antioxidant defense in nearly all cells exposed to oxygen. Her research focused on the so-called "C-terminal domain 3" (or D3), which recent research has suggested may form a D3-D3 cluster in proteins with two or four identical subunits, and which may be an important element of the copper transfer machinery.

Barry constructed mutants of the human copper chaperone for superoxide dismutase (hCCS) in order to examine more closely the possibility of the D3-D3 cluster. hCCS containing the amino acid selenocysteine was compared to naturally-occurring hCCS, and found to be similar in activity and structure. X-ray absorption spectroscopy, however, revealed that in the copper centers of the selenocysteine-containing mutants, a unique adamantane-like cluster formed between two molecules of CCS at the D3-D3 interface. These results confirm the existence of a D3-D3 copper cluster in hCCS and suggest that a unique copper cluster may exist in this protein.

"Problems in copper transport have been implicated in a number of human diseases," says Barry, a student of OHSU Professor Ninian Blackburn. "Inside cells, chaperones shuttle copper to target proteins--ones that require copper in order to do their work. Understanding the way copper is bound to a chaperone is one part of understanding the whole copper transport mechanism, which in turn may help us pinpoint what's wrong when we're faced with a disease caused by a breakdown in that mechanism."

Barry received her undergraduate degrees in Biochemistry and Biophysics and Bioresource Research at Oregon State University. After completing a Masters in Bacteriology at the University of Wisconsin-Madison, she came to OHSU in 2002 to pursue her interest in metal transport and regulation with Dr. Blackburn. She hopes to pursue her research in a post-doc position and ultimately in a professorship, with a particular focus on metal trafficking in eukaryotic cells.